Division of Cancer Survivorship, Department of Oncology, St Jude Children's Research Hospital, MS 735, 262 Danny Thomas Place, Memphis, TN 38105, USA
Department of Epidemiology and Cancer Control, St Jude Children's Research Hospital, Memphis, TN, USA.
BMJ. 2020 Jan 15;368:l6794. doi: 10.1136/bmj.l6794.
To investigate the impact of modifications to contemporary cancer protocols, which minimize exposures to cardiotoxic treatments and preserve long term health, on serious cardiac outcomes among adult survivors of childhood cancer.
Retrospective cohort study.
27 institutions participating in the Childhood Cancer Survivor Study.
23 462 five year survivors (6193 (26.4%) treated in the 1970s, 9363 (39.9%) treated in the 1980s, and 7906 (33.6%) treated in the 1990s) of leukemia, brain cancer, Hodgkin lymphoma, non-Hodgkin lymphoma, renal tumors, neuroblastoma, soft tissue sarcomas, and bone sarcomas diagnosed prior to age 21 years between 1 January 1970 and 31 December 1999. Median age at diagnosis was 6.1 years (range 0-20.9) and 27.7 years (8.2-58.3) at last follow-up. A comparison group of 5057 siblings of cancer survivors were also included.
Cumulative incidence and 95% confidence intervals of reported heart failure, coronary artery disease, valvular heart disease, pericardial disease, and arrhythmias by treatment decade. Events were graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events. Multivariable subdistribution hazard models were used to estimate hazard ratios by decade, and mediation analysis examined risks with and without exposure to cardiotoxic treatments.
The 20 year cumulative incidence of heart failure (0.69% for those treated in the 1970s, 0.74% for those treated in the 1980s, 0.54% for those treated in the 1990s) and coronary artery disease (0.38%, 0.24%, 0.19%, respectively), decreased in more recent eras (P<0.01), though not for valvular disease (0.06%, 0.06%, 0.05%), pericardial disease (0.04%, 0.02%, 0.03%), or arrhythmias (0.08%, 0.09%, 0.13%). Compared with survivors with a diagnosis in the 1970s, the risk of heart failure, coronary artery disease, and valvular heart disease decreased in the 1980s and 1990s but only significantly for coronary artery disease (hazard ratio 0.65, 95% confidence interval 0.45 to 0.92 and 0.53, 0.36 to 0.77, respectively). The overall risk of coronary artery disease was attenuated by adjustment for cardiac radiation (0.90, 0.78 to 1.05), particularly among survivors of Hodgkin lymphoma (unadjusted for radiation: 0.77, 0.66 to 0.89; adjusted for radiation: 0.87, 0.69 to 1.10).
Historical reductions in exposure to cardiac radiation have been associated with a reduced risk of coronary artery disease among adult survivors of childhood cancer. Additional follow-up is needed to investigate risk reductions for other cardiac outcomes.
ClinicalTrials.gov NCT01120353.
研究现代癌症治疗方案的改变对儿童癌症成年幸存者严重心脏结局的影响，这些改变旨在减少心脏毒性治疗的暴露并保持长期健康。
回顾性队列研究。
参与儿童癌症幸存者研究的 27 个机构。
23462 名五年幸存者（6193 名（26.4%）于 20 世纪 70 年代治疗，9363 名（39.9%）于 20 世纪 80 年代治疗，7906 名（33.6%）于 20 世纪 90 年代治疗），患有白血病、脑癌、霍奇金淋巴瘤、非霍奇金淋巴瘤、肾肿瘤、神经母细胞瘤、软组织肉瘤和骨肉瘤，诊断年龄在 21 岁之前，诊断时间为 1970 年 1 月 1 日至 1999 年 12 月 31 日。中位诊断年龄为 6.1 岁（范围为 0-20.9），最后一次随访时为 27.7 岁（8.2-58.3）。还包括 5057 名癌症幸存者的兄弟姐妹作为对照组。
按治疗年代报告心力衰竭、冠状动脉疾病、瓣膜性心脏病、心包疾病和心律失常的累积发生率和 95%置信区间。根据国家癌症研究所不良事件常见术语标准对事件进行分级。使用多变量亚分布风险模型估计每十年的风险比，并进行中介分析，以评估有和没有心脏毒性治疗暴露的风险。
心力衰竭（20 年累积发生率为 0.69%（20 世纪 70 年代治疗的患者）、0.74%（20 世纪 80 年代治疗的患者）和 0.54%（20 世纪 90 年代治疗的患者））和冠状动脉疾病（0.38%、0.24%和 0.19%，分别）的 20 年累积发生率在最近的时代有所下降（P<0.01），但瓣膜疾病（0.06%、0.06%和 0.05%）、心包疾病（0.04%、0.02%和 0.03%）或心律失常（0.08%、0.09%和 0.13%）则不然。与 20 世纪 70 年代诊断的幸存者相比，20 世纪 80 年代和 90 年代心力衰竭、冠状动脉疾病和瓣膜性心脏病的风险降低，但只有冠状动脉疾病的风险显著降低（风险比 0.65，95%置信区间为 0.45 至 0.92 和 0.53，0.36 至 0.77）。冠状动脉疾病的总体风险通过心脏辐射的调整而减弱（0.90，0.78 至 1.05），尤其是霍奇金淋巴瘤幸存者（未调整辐射：0.77，0.66 至 0.89；调整辐射：0.87，0.69 至 1.10）。
历史上减少心脏辐射的暴露与儿童癌症成年幸存者的冠状动脉疾病风险降低有关。需要进一步随访以调查其他心脏结局的风险降低。
ClinicalTrials.gov NCT01120353。
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